The principal purpose of this investigation is to evaluate the role and accuracy of radioimmunodetection in the management of colorectal cancer. Radioimmunodetection involves the administration of radioactive antibodies to tumor-specific or tumor-associated substances and the use of total-body photoscanning to visualize areas of increased radioactivity consistent with sites of antigen and tumor. The colorectal cancer-associated antigen to serve as target for radioimmunodetection will be colon-specific antigen-p (CSAp), which we have shown previously to be quantitatively increased in this tumor type. The current grant will develop radioactive CSAp antibodies (polyclonal and then affinity-purified), monoclonal (hybridoma-derived) CSAp antibodies, and Fab fragments thereof for evaluation in animal model and human studies. Year 1 of the project will involve animal localization studies using the GW-39 human tumor growing in hamsters. Localization of affinity-purified goat IgG and IgG fragments in the human tumors will be evaluated for tumor accretion, clearance, half-life, etc. Hybridomas to CSAp will also be developed. In year 2, an evaluation of the localization of the monoclonal (hybridoma) antibodies, as compared to the affinity-purified polyclonal antibody preparations, will be made. In this year, clinical studies with CSAp radioactive antibodies to assess localization of known colorectal cancers (primary and metastatic) will be undertaken. Wherever possible, comparisons will be made to the localization efficacy of antibodies to carcinoembryonic antigen (CEA), as we are now practicing this technology. Finally in year 3, more extensive clinical radioimmunodetection studies will be pursued in order to evaluate the relative efficacies of the polyclonal and monoclonal CSAp antibody preparations, or fragments thereof, for detecting and locating colorectal tumors, particularly small metastases. It is the intention of this grant to further develop the technology of radioimmunodetection for detecting and localizing colorectal cancers using a target molecule (CSAp) that, in animal studies, has appeared to be more suitable for this purpose than CEA has been. (2)